Insmed (INSM) Study Update summary

Study design and patient population

• Phase 2b randomized, double-blind, placebo-controlled trial enrolled 102 PAH patients across multiple regions, randomized 2:1 to TPIP or placebo for 16 weeks with once-daily dosing.

• 69 patients received TPIP, 33 received placebo; most were on at least one stable background PAH therapy, with a majority classified as WHO Functional Class II.

• 66% were functional class two, 80% on two background medications, representing a heavily pretreated, less symptomatic group.

• Patients titrated from 80 µg up to a maximum TPIP dose of 640 µg, with 75% reaching this dose by week five.

• 90% of TPIP patients and all placebo patients completed the study; 95% of completers enrolled in the open-label extension, where titration up to 1,280 µg is allowed.

Efficacy results

• TPIP achieved a 35% placebo-adjusted reduction in pulmonary vascular resistance (PVR) at week 16 (p<0.001), the largest ever in a controlled PAH trial.

• Six-minute walk distance improved by 35.5 meters versus placebo (p=0.003), surpassing expectations.

• NT-proBNP levels, a cardiac stress biomarker, were reduced by 60% compared to placebo (p<0.001).

• 30% of TPIP patients improved at least one WHO Functional Class versus 15% on placebo, including one patient with a two-step improvement.

• Cardiac index improved by 15% over placebo (p=0.006), with all efficacy measures trending positively and sustained benefit over the dosing period.

Safety and tolerability

• TPIP was generally well tolerated; 88–90% of TPIP patients experienced treatment-emergent adverse events, most commonly cough, headache, fatigue, chest discomfort, and flushing.

• Serious adverse events occurred in 7–7.2% of TPIP patients, with no deaths reported.

• Discontinuations due to adverse events were infrequent (4–5.8%), mostly mild; only one discontinuation was possibly drug-related.

• Cough was mild or moderate in all cases, with only one discontinuation for this reason.

• Safety profile consistent with known effects of inhaled treprostinil; no new safety signals identified.